Terpene synthases catalyze cascading 1,5-diene, or isoprene, cyclizations to create the carbocyclic backbone of terpene natural products. These enzymes promote cyclization by controlling the conformation and local electrostatic environment of a carbenium ion. The monoterpene synthases catalyze the simplest isoprene cyclizations to form the monoterpenoid class of natural products in which limonene synthase catalyzes the formation of the p-menthane subgroup from geranyl diphosphate. The negatively charged, water-soluble, tetrahedral coordination complexes of the Raymond group are proposed as a limonene synthase mimic that will catalyze the cyclization of geranyl diphosphate derivatives to p-menthane monoterpenoids. Development of the system will provide a relatively simple model for the intracavity environment of limonene synthase and yield a physical description of the interaction between the substrate and cavity, The coordination cage complexes have catalyzed transformations that required either conformational or environmental control over encapsulated intermediates. Therefore, the complexes are proposed to catalyze a biomimetic isoprene cyclization that requires both aspects of reaction control. Specifically, the tetrahedral coordination complex will catalyze the cyclization of nerol or linalool derived substrates as surrogates for geranyl diphosphate. Catalysis should occur within the negatively-charged cavity of the complex driven by hydrophobic encapsulation. Binding will organize substrate conformation, while the negatively charged cavity stabilizes the cationic cyclization intermediates. Encapsulation of the carbenium ion will inhibit rearrangements to monoterpenoids outside of the p-menthane family. This strategy will provide a proof of principle for controlling a carbenium ion by supramolecular encapsulation, serve as the first example of a functional terpene synthase mimic, and probe simple encapsulation as an enzymatic strategy for catalysis. PUBLIC HEALTH RELEVANCE Mimicking enzyme function is an important task for not only validating biochemical models of action, but developing new concepts of small molecule catalysis. A tetrahedral, coordination cage complex is proposed to mimic the function of a class of enzymes known as the monoterpene synthases. Binding of acyclic terpene precursors within the complex's negatively-charged cavity will catalyze their cationic cyclization to the p-menthane family of monoterpenoids in a biomimetic fashion. [unreadable] [unreadable] [unreadable]